Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated ...concern about immune evasion and the duration of protection from vaccines in children and adolescents.
Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age.
We enrolled 1185 case patients (1043 88% of whom were unvaccinated, 291 25% of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval CI, 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days).
BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.).
The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age.
We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative).
A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval CI, 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated.
Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).
Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants.
We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022).
A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 12% received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval CI, 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.
Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).
Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may affect risk for developing ...gestational diabetes mellitus (GDM). While previous systematic reviews have been conducted on this topic, they did not assess internal validity of the included studies and their search strategies were narrowly focused.
The objective of this study is to assess the effect of higher PFAS exposure (defined by individual compounds or mixtures measured before or during pregnancy) on GDM and subclinical measures of impaired glucose homeostasis (measured during pregnancy) compared to lower PFAS exposure in pregnant.
We developed our systematic review protocol in accordance with the Navigation Guide. Peer-reviewed journal and grey literature searches were piloted in to identify relevant studies and refine our search terms and strategy. We also piloted the study screening criteria and data extraction form in DistillerSR, and refined our protocol accordingly. The risk of bias assessment protocol was adapted from Navigation Guide guidance and will be piloted and performed in DistillerSR. Pending the identification of comparable studies, quantitative meta-analyses will be performed where possible. Study results that cannot be quantitatively synthesized will be included in a narrative synthesis. The quality and strength of the body of evidence will be evaluated using Navigation Guide methodology, which is informed by guidance from the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also made refinements to the quality of evidence considerations based on guidance from the National Institute of Environmental Health Sciences (NIEHS) Office of Health Assessment and Translation (OHAT).
This work was supported by the Systematizing Data on Per- and Polyfluoroalkyl Substances and Health Northeastern University TIER 1 Award.
Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. ...Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood.
In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression.
We compared 304 MIS-C case-patients (280 92% unvaccinated) with 502 controls (346 69% unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR aOR: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated.
Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.
Abstract
Background
Severe critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested ...differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test the hypothesis that hydrocortisone will be differentially associated with clinical outcomes in children with or without immunoparalysis.
Methods
Children with severe sepsis/septic shock underwent blood sampling within 48 h of sepsis onset. Immune function was measured by quantifying whole blood ex vivo LPS-induced TNFα production capacity, with a TNFα response < 200 pg/ml being diagnostic of immunoparalysis. The primary outcome measure was number of days in 14 with MODS. Univariate and multivariable negative binomial regression models were used to examine associations between hydrocortisone use, immune function, and duration of MODS.
Results
One hundred two children were enrolled (age 75 6–160 months, 60% male). Thirty-one subjects received hydrocortisone and were more likely to be older (106 52–184 vs 38 3–153 months,
p
= 0.04), to have baseline immunocompromise (32 vs 8%,
p
= 0.006), to have higher PRISM III (13 8–18 vs 7 5–13,
p
= 0.0003) and vasoactive inotrope scores (20 10–35 vs 10 3–15,
p
= 0.0002) scores, and to have more MODS days (3 1–9 vs 1 0–3,
p
= 0.002). Thirty-three subjects had immunoparalysis (TNFα response 78 52–141 vs 641 418–1047 pg/ml,
p
< 0.0001). Hydrocortisone use was associated with longer duration of MODS in children with immunoparalysis after adjusting for covariables (aRR 3.7 1.8–7.9,
p
= 0.0006) whereas no association with MODS duration was seen in children without immunoparalysis (aRR 1.2 0.6–2.3,
p
= 0.67).
Conclusion
Hydrocortisone use was independently associated with longer duration of MODS in septic children with immunoparalysis but not in those with more robust immune function. Prospective clinical trials using a priori immunophenotyping are needed to understand optimal hydrocortisone strategies in this population.
Multisystem inflammatory syndrome in children (MIS-C) represents a hyperinflammatory state that can result in multi-organ dysfunction and death. Myeloid-derived suppressor cells (MDSC) are an ...immunosuppressive cell population that expands under inflammatory conditions and suppresses T cell function. We hypothesized that MDSC would be increased in children with MIS-C and that MDSC expansion would be associated with T cell lymphopenia.
We conducted a prospective, observational study. Initial blood samples were collected within 48 h of admission. Age-matched healthy controls underwent sampling once. MDSC and T cell populations were identified by flow cytometric methods.
We enrolled 22 children with MIS-C (12 ICU, 10 ward) and 21 healthy controls (HC). Children with MIS-C demonstrated significantly higher MDSC compared to HC, and MDSC expansion persisted for >3 weeks in the ICU group. Children with MIS-C admitted to the ICU demonstrated significantly lower absolute numbers of T cells and natural killer cells. There were no significant associations between MDSC and cardiac dysfunction, duration of hospitalization, or vasoactive inotrope score.
Our study suggests that children critically ill with MIS-C have expansion of MDSC and associated decreased T cell and NK cell populations. Our results did not demonstrate associations between MDSC and clinical outcomes.
Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated immune response occurring several weeks after SARS-CoV-2 infection that can result in multi-organ dysfunction and death. Children severely ill with MIS-C demonstrated increased myeloid-derived suppressor cells and decreased absolute numbers of CD4+ and CD8 + T cells and NK cells compared to healthy controls. There was no significant association between MDSC numbers and clinical outcomes; including cardiac dysfunction, length of stay, or requirement of vasoactive support, in children with MIS-C.
Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with ...SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5),
and real-world studies in persons aged 12-18 years demonstrated high vaccine effectiveness (VE) against severe COVID-19 (6). Recent evidence suggests that COVID-19 vaccination is associated with lower MIS-C incidence among adolescents (7); however, VE of the 2-dose Pfizer-BioNTech regimen against MIS-C has not been evaluated. The effectiveness of 2 doses of Pfizer-BioNTech vaccine received ≥28 days before hospital admission in preventing MIS-C was assessed using a test-negative case-control design
among hospitalized patients aged 12-18 years at 24 pediatric hospitals in 20 states** during July 1-December 9, 2021, the period when most MIS-C patients could be temporally linked to SARS-CoV-2 B.1.617.2 (Delta) variant predominance. Patients with MIS-C (case-patients) and two groups of hospitalized controls matched to case-patients were evaluated: test-negative controls had at least one COVID-19-like symptom and negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) or antigen-based assay results, and syndrome-negative controls were hospitalized patients without COVID-19-like illness. Among 102 MIS-C case-patients and 181 hospitalized controls, estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI = 78%-97%). All 38 MIS-C patients requiring life support were unvaccinated. Receipt of 2 doses of the Pfizer-BioNTech vaccine is associated with a high level of protection against MIS-C in persons aged 12-18 years, highlighting the importance of vaccination among all eligible children.
In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young ...children hospitalized for acute COVID-19.
We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization.
Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died.
Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.
PDF
